Who considers leukoreduced cellular blood products equivalent to those made from CMV seronegative donors?

Does your facility consider leukoreduced cellular blood products to be 'equivalent' to CMV-seronegative cellular blood products, with regards to transfusion transmitted CMV risk? If so, are there any restrictions- e.g. do you also accept them for the low birth weight neonate and the bone marrow transplant patient?

To which the following replies have been received:

1. According to a major blood provider in the San Francisco area, almost all of the hospitals in the East and South San Francisco Bay area consider CMV seronegative and leukocyte reduced blood products equivalent and would consider them equivalent for all patients.  This includes the tertiary care Children's Hospital of Oakland. Some of the other hospitals are still a little leery about low birth weight neonates as the major studies have been in bone marrow and leukemia patients and not neonates.
   
   
2. A centralized transfusion service supporting 11 area hospitals (3 neonatal intensive care units totaling >100 beds), reports that they transfuse 22,000 leukocyte reduced red cells, 2500 leukocyte reduced single donor plateletpheresis units, and 15,000 leukocyte reduced platelet concentrates annually. This transfusion service considers leukocyte reduced blood products as CMV safe and equivalent to CMV seronegative for all patient groups EXCEPT CMV-seronegative paired allogeneic stem cell transplant recipients and small bowel transplant recipients.
   
   
3. A very prestigious medium-sized facility in Bethesda, Maryland uses leukoreduced blood products and CMV-seronegative blood products interchangeably. The facility transfuses about 4,500 components annually to transplant recipients, but none to neonates.
   
   
4. A 300-bed transfusion service reports that they transfuse between 400-500 red blood cell products/month, and that 100% of the RBCs they transfuse to patients with leukemia who are potential bone marrow transplant candidates are CMV-seronegative, prestorage leukoreduced and irradiated. All platelet products for these patients are irradiated. This transfusion service uses both apheresis platelets and platelet concentrates. The apheresis platelets are prestorage leukoreduced. The transfusion service tries to use CMV seronegative blood whenever possible, but if it is not available and if the heme-onc physicians are willing to accept leukocyte reduced products as CMV safe, they will use leukocyte reduced products in place of CMV seronegative. 100% of the whole blood platelets are CMV seronegative since they do not consider bedside filtration [at their facility, at least] to be CMV safe. This transfusion service realizes that the Bowden study in Seattle was based on bedside filtration, but that the Bowden study was in a controlled, research environment and they had better control over the filter training than did this hospital in their environment. Currently, a proposal to move to "CMV safe" products is being considered by the transfusion committee. This transfusion service does not transfuse neonates routinely - only on an emergency basis. On the rare occasion when they do transfuse a neonate they provide CMV seronegative, irradiated, prestorage leukoreduced products.
   
   
5. A recently retired blood banker from the Chicago area reports that at his hospital transfusion service in Chicago, where mainly adult patients were treated, bedside filtered, ‘leukocyte reduced’ blood products were not regarded equivalent to CMV seronegative blood products. However at a children's' hospital with a large bone marrow transplant service where they used laboratory filtration with QC that was always well below maximum allowable WBC levels, the intra-laboratory leukoreduced blood products were considered equivalent to CMV seronegative. Close to 100 bone marrow recipients were treated with the leukoreduced blood products without evidence of transfusion transmitted CMV disease.
   
   
6. A medium-sized transfusion service in the San Fernando Valley of Southern California reports that they transfuse about 150 units to neonatal patients but very few to transplant patients. This facility does NOT consider CMV seronegative units equivalent to leukoreduced units. They do, however, use leukoreduced units in lieu of CMV seronegative units when CMV seronegative units are not readily available. This facility wanted the e-network to consider very carefully that if one places any restrictions whatsoever on the use of non-CMV tested leukoreduced units (e.g. if you do not accept leukoreduced units not tested for CMV for neonates or transplant patients), then you cannot consider these products as equivalent.
   
   
7. A transfusion service in Pennsylvania (affiliated with a famous college football team) considers leukoreduced blood components to be equivalent to those testing seronegative for CMV. This is without exception. The transfusion service is in a university hospital of approximately 425 beds with pediatric and neonatal intensive care services, as well as full adult services with solid organ and bone marrow transplant programs.
   
   
8. A rather well known very large academic, tertiary care center in Ohio reports that they supply leukocyte reduced blood products to all neonates and all pediatric heme-onc patients. This facility considers leukoreduced cellular blood products to be 'equivalent' to CMV-seronegative cellular blood products, with regard to transfusion transmitted CMV risk. The only exception is for directed donors whose blood might be used repeatedly in pediatric bone marrow transplant patients. In such cases, the clinician may specifically request CMV seronegative blood. And, if the directed donor is CMV seropositive, the clinician may disqualify such a donor.
   
   
9. A facility in California, known for its tree mascot reports that for RBC transfusion, their hospital considers in-lab leukoreduced RBC as CMV safe (i.e., filtered at the collectioncenter or in the transfusion service). However, the majority of "CMV safe" RBC used are antibody negative. Filtration is used primarily to render an antibody positive product "CMV safe" if that product is specifically needed for a patient with a "CMV neg." special need. The facility reports that for platelets that their hospital has not yet accepted leukoreduced platelets as equivalent to CMV seronegative. This is because the level of confidence in the leukoreduction process for platelets remains under question. The responder to this question suspects that the hospital will eventually change its policy, but the data on pheresis leukoreduction QC have not yet been presented to the Transfusion Committee for review.
   
   
10. An 800-bed hospital with >35,000 RBC and >12,000 platelet transfusions annually reports that they consider prestorage leukoreduced blood products as equivalent to CMV-negative in their large transfusion service. This applies for all indications for CMV seronegative blood products.
    
    
11. A transfusion service reported that they do not use the word equivalent in their statement. The statement that they use when they substitute is "A leukocyte reduced component has been substituted for a CMV seronegative blood component". If they are asked if filtered products are equivalent to CMV negative, they say that filtered products are CMV safe. They substitute filtered units for all of the pediatric units. They also make substitution for the bone marrow patients that are CMV negative.

ADDENDA Jan. 24, 2001

12. It is distressing to me that the anecdotal approach is being used to address this issue. What one can get away with in large populations containing only a very small number of patients at highest risk is hardly proof that the most vulnerable will not suffer. The vast majority of recipients identified in those settings cited are not at risk. This is kind of the reverse of a "sentinel chicken" approach to safety. Almost none of the centers you cite have any significant numbers of the highest risk patients. For bone marrow transplantation these would include only allogeneic transplant recipients when both donor and recipient were CMV negative. For this reason the FACT standards REQUIRE that for accreditation for allogeneic transplantation a center must have CMV negative blood products available 24 hours a day. This is not intended to be interpreted except as from CMV antibody negative donors. We have very sensitive techniques for determining the level of CMV in blood products. A modest scale CMV PCR study of CMV antibody positive blood products which have been "pre-storage leuko-reduced" randomly selected from blood banks without pre-notification of the supplier could easily provide an answer as to whether there is potential for transmission. A comparison with CMV antibody negative products which have or have not been pre-storage leuko-reduced would be of interest. Further requirements that monitoring be performed either by blood banks or suppliers and notification of recipients of changes in procedures as part of contracts would be appropriate even if such a study were consistent with the hypothesis that these products were safe to supply as CMV negative.
    
    (The individual submitting the above comment was asked for clarification regarding institutional accreditation by FACT, in the event that an institution chose to use leukoreduced blood products as CMV low risk and not to use CMV seronegative blood products. Here is what was said:)

    As a founding member of FAHCT, I can assure you of the intent of the FAHCT standards. You should obtain a copy for yourself. I believe that the standard actually says "components suitable for CMV negative recipients". It certainly is incorrect to say "leukoreduced blood products are considered equivalent to CMV antibody negative", unless you say by whom and what "considered equivalent" means as opposed to being "demonstrated to be" for particularly vulnerable populations. We are finding that physicians are being supplied with pre-storage leuko-reduced products when requesting CMV negative without knowing that they are not antibody negative. I wonder how many of your network members have agreement from their ordering physicians with their assertions. All I am suggesting is that proper validation of this hypothesis needs to be done to demonstrate the safety of these products in the field and that ongoing monitoring of safety needs to be in place. All of us in the transplant community are very concerned about the blood supply sufficiency, safety and cost. It is very important that we be reassured that the blood banking community has adequately tested an hypothesis rather than simply stating the conclusion as "considered as".

    Editor's Note: It is ironic that this comment was submitted to the e-Network at the same time that the FDA was publishing their DRAFT guidance for use of Leukoreduced Blood (Jan. 23, 2001). To see the draft document and draw your own conclusions as to the appropriateness of using leukoreduced blood to prevent CMV transmission, please go to FDA issues updated draft Guidance for Industry on Prestorage Leukoreduction. It is my suspicion that FACT (formerly FAHCT)-accredited institutions are using leukoreduced blood products to prevent CMV transmission, and not requiring that all products be CMV seronegative, as suggested by the individual whose comment is above.

Editor's ADDENDA Feb. 3, 2001

13. In case any e-network member is unaware of FAHCT, it is a nonprofit corporation developed by the International Society of Hematotherapy and Graft Engineering (ISHAGE) and the American Society of Blood and Marrow Transplantation (ASBMT) for the purposes of self-assessment and accreditation in the field of hematopoietic cell therapy. This organization has initiated a voluntary comprehensive standard-setting, inspection and accreditation program that encompasses all phases of hematopoietic collection, processing and transplant. FAHCT has established standards for the provision of quality medical and laboratory practice in hematopoietic cell transplantation; conducts inspections, and accredits programs that will encourage health institutions and facilities performing hematopoietic cell transplantation to voluntarily meet these standards; and recognizes compliance with standards by issuance of Certificates of Accreditation. In light of what the e-Network has been told, it would be interesting to know if all of the FACT-accredited institutions have CMV-negative blood products available 24 hours a day, or if any of these institutions use leukocyte-reduced blood products as equivalent to CMV-seronegative.
    
    In addition to the above information, the following comments (some slightly edited) have been received for posting on this topic:
    
    
14. I am writing about the CMV issue and FACT. The American Society for Blood and Marrow Transplantation (ASBMT; http://www.asbmt.org/), the CDC, and the Infectious Diseases Society of America just published in MMWR and in the ASBMT journal (Biology of Blood and Marrow Transplantation 2000:6;665) their guidelines for treating BMT patients. In these guidelines, they clearly state that leukocyte-reduced blood products OR CMV-seronegative should be provided. Since ASBMT often reflects FAHCT policy, I believe that FAHCT allows (at least in this most recent publication) leukocyte-reduced blood (presumably by cGMP and prestorage), as equal to CMV-safe. That's what we do at Yale for all patients. We are 100% ULR and do not CMV serotest anymore (since mid 1999).
    
    
15. Our transfusion service in Ohio regards laboratory leukoreduced blood components equivalent to CMV seronegative components in the provision of CMV-safe transfusion components. We use these components interchangeably for all transfusion recipients including neonates and hematologic transplants. The transfusion service is medium-sized at a children's hospital. Rough estimate on component use annually: these are all leukoreduced....Transplants: 1800 RBC, 7200 random donor platelets, 720 apheresis platelets; neonates - 500 transfusion episodes.
    
    
16. Regarding patients at high risk for CMV infection ... everyone involved in the discussion regarding CMV should understandthat the term "CMV-negative" is an unfortunate one. The term means, of course, "serologically negative" using a rather low performance latex agglutination test or other test. A substantial minority of units which are CMV-negative harbor CMV virus. Everyone should understand the limitations of the, so-called, "gold standard".

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